Phase II Trial of Atezolizumab Combined With Carboplatin and Pemetrexed for Patients With Advanced Nonsquamous Non–Small-Cell Lung Cancer With Untreated Brain Metastases (Atezo-Brain, GECP17/05)

Author(s): Ernest Nadal, MD, PhD1,2; Delvys Rodríguez-Abreu, MD3; Marta Simó, MD, PhD4; Bartomeu Massutí, MD, PhD5; Oscar Juan, MD, PhD6; Gerardo Huidobro, MD7; Rafael López, MD8; Javier De Castro, MD, PhD9; Anna Estival, MD, PhD10; Joaquín Mosquera, MD11; Ivana Sullivan, MD, PhD12; Enriqueta Felip, MD, PhD13; Ana Blasco, MD14; Maria Guirado, MD15; Eva Pereira, BoS16; Noelia Vilariño, MD1,2,4; Valentín Navarro, PhD1; and Jordi Bruna, MD, PhD4
Source: DOI: 10.1200/JCO.22.02561 Journal of Clinical Oncology 41, no. 28 (October 01, 2023) 4478-4485

Dr. Anjan Patel's Thoughts

A nicely done Spanish study showing that in metastatic NSCLC, asymptomatic patients with brain metastases can have radiation therapy deferred. Starting with systemic therapy was found to be reasonable and effective, validating a common practice. Patients were treated with atezolizumab + carboplatin + pemetrexed + steroids, and any number of brain mets was allowed as long as they had at least one 10mm in size or greater. This study excluded patients harboring EGFR/ALK driver mutations.

PURPOSE

The Atezo-Brain study evaluated atezolizumab combined with chemotherapy in patients with advanced non–small-cell lung cancer (NSCLC) with untreated brain metastases, a population traditionally excluded from trials.

METHODS

This single-arm phase II clinical trial enrolled patients with advanced nonsquamous NSCLC with untreated brain metastases without neurologic symptoms or asymptomatic with medical treatment. Dexamethasone was allowed up to 4 mg once daily. Atezolizumab plus carboplatin and pemetrexed was given for four to six cycles followed by atezolizumab plus pemetrexed until progression for a maximum of 2 years. The primary end points were to determine the progression-free survival (PFS) rate at 12 weeks and the incidence of grade ≥3 adverse events during the first 9 weeks. Intracranial outcomes were assessed using response assessment in neuro-oncology brain metastases criteria.

RESULTS

Forty patients were enrolled and 22 (55%) were receiving corticosteroids at baseline. The overall 12-week PFS rate was 62.2% (95% credibility interval [CrI], 47.1 to 76.2). The rate of grade 3/4 adverse events during the first 9 weeks was 27.5%. Most neurologic events were grade 1 and 2 but five patients (12.5%) experienced grade 3-4 neurologic events. With a median follow-up of 31 months, intracranial median PFS was 6.9 months and response rate was 42.7% (95% CrI, 28.1 to 57.9). Systemic median PFS was 8.9 months and response rate was 45% (95% CrI, 28.1 to 57.9). The median overall survival (OS) was 11.8 months (95% CI, 7.6 to 16.9) and the 2-year OS rate was 27.5% (95% CI, 16.6 to 45.5).

CONCLUSION

Atezolizumab plus carboplatin and pemetrexed demonstrates activity in patients with advanced nonsquamous NSCLC with untreated brain metastases with an acceptable safety profile.

Author Affiliations

1Department of Medical Oncology, Institut Català d’Oncologia (ICO), L’Hospitalet de Llobregat, Barcelona, Spain; 2Preclinical and Experimental Research in Thoracic Tumors (PReTT) Group, Oncobell Program, Bellvitge Biomedical Research Institute (IDIBELL), L’Hospitalet de Llobregat, Barcelona, Spain; 3Department of Medical Oncology, Complejo Hospitalario Universitario Insular-Materno Infantil de Gran Canaria, Universidad de Las Palmas de Gran Canaria, Las Palmas de Gran Canaria, Spain; 4Neuro-Oncology Unit, Hospital Universitari de Bellvitge-ICO, IDIBELL, L’Hospitalet, Barcelona, Spain; 5Department of Medical Oncology, Hospital General de Alicante, Alicante, Spain; 6Department of Medical Oncology, Hospital Universitari La Fe, Valencia, Spain; 7Department of Medical Oncology, Complejo Hospitalario Universitario de Vigo, Vigo, Spain; 8Department of Medical Oncology, Hospital Clínico de Valladolid, Valladolid, Spain; 9Department of Medical Oncology, Hospital Universitario La Paz, Madrid, Spain; 10Department of Medical Oncology, Institut Català d’Oncologia (ICO), Badalona, Spain; 11Department of Medical Oncology, Hospital Universitario A Coruña, A Coruña, Spain; 12Department of Medical Oncology, Hospital Sant Pau, Barcelona, Spain; 13Department of Medical Oncology, Vall d’Hebron University Hospital, Vall d’Hebron Institute of Oncology, Barcelona, Spain; 14Department of Medical Oncology, Hospital General de Valencia, Valencia, Spain; 15Department of Medical Oncology, Hospital Universitario de Elche, Elche, Spain; 16Spanish Lung Cancer Group, Barcelona, Spain

Leave a Comment

Your email address will not be published. Required fields are marked *

Related Articles

Neoadjuvant Osimertinib for Resectable EGFR-Mutated Non–Small Cell Lung Cancer

The phase III NeoADAURA trial evaluated neoadjuvant osimertinib (OSI) with or without platinum-based chemotherapy (CT) versus CT alone in resectable, EGFR-mutated stage II-IIIB non-small cell lung cancer (NSCLC). Both OSI+CT and OSI monotherapy significantly improved major pathologic response (MPR: 26% and 25% vs 2%), and 12-month event-free survival (EFS) rates were higher with OSI-containing regimens (OSI+CT 93%, OSI 95%, CT 83%). Nodal downstaging was also more frequent with OSI arms (53% vs 21%). Neoadjuvant OSI—with or without CT—looks like a real step forward for our EGFR-mutant NSCLC patients, especially given the robust pathologic responses and high rates of surgical completion.

Read More »

Phase III Study of Mediastinal Lymph Node Dissection for Ground Glass Opacity–Dominant Lung Adenocarcinoma

This large, well-done study compared systematic mediastinal lymph node dissection (LND) versus no LND in patients with GGO-dominant invasive lung adenocarcinoma (CTR ≤0.5, ≤3 cm, cT1N0M0). Interim analysis of 302 patients showed no lymph node metastases in either arm, with both groups achieving 3-year disease-free survival (DFS) and overall survival (OS) of 100% at the time of analysis. The no LND arm had significantly shorter surgery duration (74 vs 109 min), less blood loss (44 vs 82 mL), shorter hospital stays (3.9 vs 4.5 days), and fewer grade ≥2 complications (3.3% vs 9.3%). Based on these findings, the trial was terminated early for nonmaleficence, and the authors recommend omitting systematic mediastinal LND in this population. In short, for carefully selected GGO-dominant lung adenocarcinoma, skipping mediastinal LND appears safe and spares patients’ unnecessary morbidity—this could be a real practice-changer for our early-stage, node-negative cases.

Read More »

Overall Survival with Amivantamab–Lazertinib in EGFR-Mutated Advanced NSCLC

The phase 3 MARIPOSA trial compared amivantamab–lazertinib (Ami-Laz) to osimertinib (Osi) in untreated EGFR-mutated advanced non-small cell lung cancer (NSCLC), showing a significant overall survival (OS) benefit for Ami-Laz (3-yr OS was 60% vs 51%). Median OS was not reached for Ami-Laz vs 36.7 months for Osi, with a projected >12-month median OS advantage. Ami-Laz also improved time to symptomatic progression (43.6 vs 29.3 months) and showed durable intracranial control, though grade ≥3 adverse events (AEs) were higher (80% vs 52%), notably skin, venous thromboembolism (VTE), and infusion reactions. In short, Ami-Laz is emerging as a new standard for first-line EGFRm NSCLC, but we’ll need to be proactive about managing its toxicity profile in clinic and whether this is superior or equivalent to Osi + chemo is currently unclear.

Read More »

Adagrasib versus docetaxel in KRASG12C-mutated non-small-cell lung cancer (KRYSTAL-12): a randomised, open-label, phase 3 trial

Adagrasib demonstrated a median progression-free survival (PFS) of 5.5 months compared to 3.8 months with docetaxel in patients with KRAS G12C-mutated tumors. Treatment-related adverse events occurred in 47% of patients receiving Adagrasib and 46% in the docetaxel group. In my experience, Adagrasib is also more tolerable, making it a favorable option for this patient population.

Read More »